Designed Ankyrin Repeat Proteins as Her2 Targeting Domains in Chimeric Antigen Receptor-Engineered T Cells.
Designed Ankyrin Repeat Proteins as Her2 Targeting Domains in Chimeric Antigen Receptor-Engineered T Cells.
复制标题
DOI：
10.1089/hum.2017.021
复制
发表时间：
2017-09
影响因子：
4.2
通讯作者：
Elizabeth L. Siegler;Si Li;Y. J. Kim;Pin Wang
中科院分区：
文献类型：
--
作者：
Elizabeth L. Siegler;Si Li;Y. J. Kim;Pin Wang
嵌合抗原受体（CAR）工程是癌症免疫治疗的一个分支，它使免疫细胞利用抗体衍生的单链可变片段（scFvs）靶向细胞表面表达的肿瘤抗原。然而，其他抗体模拟物，如设计的锚蛋白重复序列蛋白（DARPins），也可以作为car中的抗原结合域。本研究表明，利用靶向Her2的DARPins G3和929的CAR-T细胞在体外可以像使用scFv 4D5的CAR-T细胞一样有效地靶向人表皮生长因子受体2 （Her2）过表达的癌细胞，并且G3 CAR-T细胞在体内可以像4D5 CAR-T细胞一样有效地减缓或消除肿瘤的生长。一些DARPin可能为car中scFv的使用提供了一个有吸引力的替代方案，因为它们更小，热力学稳定，免疫原性差，并且可以从DARPin库中生成具有不同结合特性的DARPin。
Chimeric antigen receptor (CAR) engineering is a branch of cancer immunotherapy that equips immune cells to target tumor antigens expressed on the cell surface using antibody-derived single-chain variable fragments (scFvs). However, other antibody mimetics, such as designed ankyrin repeat proteins (DARPins), can also serve as antigen-binding domains in CARs. This study shows that CAR-engineered T (CAR-T) cells utilizing Her2-targeting DARPins G3 and 929 can target human epidermal growth factor receptor 2 (Her2)-overexpressing cancer cells as effectively as CAR-T cells with the scFv 4D5 in vitro, and G3 CAR-T cells can slow or eliminate tumor growth in vivo as effectively as 4D5 CAR-T cells. Some DARPins may offer an attractive alternative to scFv usage in CARs, as they are smaller, thermodynamically stable, poorly immunogenic, and can be generated with different binding properties from DARPin libraries.